Synthesis of new thiophene and benzo[b]thiophene hydrazide derivatives as human NPY Y(5) antagonists.

abstract：:A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dickerson TJ,Reed NN,Janda KD

更新日期：2001-06-18 00:00:00

abstract：:4-Thiazolidinone derivatives were synthesized using T3P®-DMSO media as a cyclodehydrating agent. All the molecules were tested for their cytotoxicity against leukemic cell lines. The compound 3-(4-bromophenyl)-2-(4-(dimethylamino)phenyl)thiazolidin-4-one (4e) with electron donating substituent at para position of phen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharath Kumar KS,Hanumappa A,Vetrivel M,Hegde M,Girish YR,Byregowda TR,Rao S,Raghavan SC,Rangappa KS

更新日期：2015-09-01 00:00:00

abstract：:To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P(2)-P(3) amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Greenspan PD,Clark KL,Cowen SD,McQuire LW,Tommasi RA,Farley DL,Quadros E,Coppa DE,Du Z,Fang Z,Zhou H,Doughty J,Toscano KT,Wigg AM,Zhou S

更新日期：2003-11-17 00:00:00

abstract：:A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P(1) hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P(1) moiety. Replacement of the benzothiophene with different heterocyclic sy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Nemoto PA,Kim JM,Hao MH,Qian KC,Farrow NA,Albaugh DR,Fowler DM,Schneiderman RD,Michael August E,Martin L,Hill-Drzewi M,Pullen SS,Takahashi H,De Lombaert S

更新日期：2011-08-01 00:00:00

abstract：:Here we present first dinucleotide affinity resins for purification of proteins that specifically recognize the 5' end of mRNA. Constructed resins possess either a naturally occurring mono- or trimethylated cap or their analogues resistant towards enzymatic degradation, bearing a CH(2) bridge between β and γ position ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jankowska-Anyszka M,Piecyk K

更新日期：2011-10-15 00:00:00

abstract：:Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Richardson BG,Jain AD,Speltz TE,Moore TW

更新日期：2015-06-01 00:00:00

abstract：:Regiospecific synthesis of 2,3-disubstituted-L-histidines and 2,3-disubstituted histamines starting from L-histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Narayanan S,Vangapandu S,Jain R

更新日期：2001-05-07 00:00:00

abstract：:A pilot library of novel 4,4,5,5-tetramethyl-2-(4-substitutedstyrylphenyl)-1,3,2 dioxaborolane derivatives has been synthesized. 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaboratophenyl)-methyl triphenylphosphonium bromide 3 was treated with various aldehydes in the presence of 3 equiv of (t)BuONa in DMF, and stirred at room te...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das BC,Zhao X,Tang XY,Yang F

更新日期：2011-09-15 00:00:00

abstract：:The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

更新日期：2004-08-02 00:00:00

abstract：:We report the first synthesis of the C-terminally spermine-conjugated stapled peptide-based inhibitors of the p53-Mdm2 interaction. Subsequent biological, biophysical and cellular uptake assays with the spermine-conjugated stapled peptides revealed that spermine conjugation minimally affects biological activity while ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Muppidi A,Li X,Chen J,Lin Q

更新日期：2011-12-15 00:00:00

abstract：:The interactions of some natural flavonols with alpha, beta- and gamma-Cds have been investigated. Guest molecules were galangin, kaempferol and quercetin. Inclusion complexes were prepared by kneading and freeze-drying. The complexes were characterized using different physico-chemical methods based on differential sc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bergonzi MC,Bilia AR,Di Bari L,Mazzi G,Vincieri FF

更新日期：2007-11-01 00:00:00

abstract：:Series of short amino terminal modified cationic peptides were designed and synthesized. All of the synthesized compounds were tested against gram-positive as well as gram-negative bacterial strain. Some of the compounds exhibit potent antibacterial activity and no hemolytic activity even at high dose level (1000 micr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bisht GS,Rawat DS,Kumar A,Kumar R,Pasha S

更新日期：2007-08-01 00:00:00

abstract：:The mechanism of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) to scavenge DPPH radical is clarified by density functional theory (DFT) calculations. It is revealed that H-atom-abstraction rather than electron-transfer reaction is involved in the radical-scavenging process of edaravone, and H-atom at position 4 is r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang LF,Zhang HY

更新日期：2003-11-03 00:00:00

abstract：:A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chloroph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahsan MJ,Govindasamy J,Khalilullah H,Mohan G,Stables JP

更新日期：2012-12-01 00:00:00

abstract：:The inhibition of the newly discovered cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozyme XIII of murine origin (mCA XIII) has been investigated with a series of anions, such as the physiological ones (bicarbonate, chloride), or the metal complexing anions (cyanate, cyanide, azide, hydrogen sulfide, etc), nitrate, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Lehtonen JM,Parkkila S,Scozzafava A,Supuran CT

更新日期：2004-11-01 00:00:00

abstract：:Incubation of epicubenol synthase with farnesyl pyrophosphate in the presence of 11.1 atom% H2(18)O gave epicubenol (2) in which the hydroxyl oxygen atom was shown to be derived exclusively from water, as established by GC-selected ion monitoring MS of the derived TMS-epicubenol derivative (15). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cane DE,Ke N

更新日期：2000-01-17 00:00:00

abstract：:Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller LM,Mayer SC,Berger DM,Boschelli DH,Boschelli F,Di L,Du X,Dutia M,Floyd MB,Johnson M,Kenny CH,Krishnamurthy G,Moy F,Petusky S,Tkach D,Torres N,Wu B,Xu W

更新日期：2009-01-01 00:00:00

abstract：:The discovery of a series of novel and orally efficacious type II calcimimetics, developed from the lead compound 1, is described herein. Compound 22 suppressed plasma PTH levels relative to vehicle when dosed orally in a rat pharmacodynamic model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harrington PE,St Jean DJ Jr,Clarine J,Coulter TS,Croghan M,Davenport A,Davis J,Ghiron C,Hutchinson J,Kelly MG,Lott F,Lu JY,Martin D,Morony S,Poon SF,Portero-Larragueta E,Reagan JD,Regal KA,Tasker A,Wang M,Yang Y,

更新日期：2010-09-15 00:00:00

abstract：:Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the structure, potential ligand-protein binding interactions, and pharm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Galatsis P,Henderson JL,Kormos BL,Han S,Kurumbail RG,Wager TT,Verhoest PR,Noell GS,Chen Y,Needle E,Berger Z,Steyn SJ,Houle C,Hirst WD

更新日期：2014-09-01 00:00:00

abstract：:Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) receptors. Several members of this group showed excellent pharmacokinetic and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agai-Csongor E,Domány G,Nógrádi K,Galambos J,Vágó I,Keserű GM,Greiner I,Laszlovszky I,Gere A,Schmidt E,Kiss B,Vastag M,Tihanyi K,Sághy K,Laszy J,Gyertyán I,Zájer-Balázs M,Gémesi L,Kapás M,Szombathelyi Z

更新日期：2012-05-15 00:00:00

abstract：:New analogues of the venerable antimalarial drug primaquine have been synthesized and bioassayed in vivo against Pneumocystis carinii, a life-threatening infection common among immunosuppressed patients. Two of these new compounds are significantly more active than primaquine itself, and provide new information for fu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Goodwin TE,Boylan CJ,Current WL,Byrd JC,Edwards CB,Fuller DA,Green JL,Larocca CD,Raney KD,Ross AS,Tucker WA

更新日期：2000-10-02 00:00:00

abstract：:A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as novel melatoninergic ligands. Binding affinity assays were performed on cloned human MT(1) and MT(2) receptors, stably expressed in NIH3T3 cells. Compound 16 was identified as an orally bioavailable agonist at MT(1) and MT(2) melatonin rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun LQ,Chen J,Mattson RJ,Epperson JR,Deskus JA,Li WS,Takaki K,Hodges DB,Iben L,Mahle CD,Ortiz A,Molstad D,Ryan E,Yeleswaram K,Xu C,Luo G

更新日期：2003-12-15 00:00:00

abstract：:We report the preliminary results of the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a number of phenyl alkyl imidazole-based compounds as inhibitors of the two components of 17alpha-hydroxylase/17,20-lyase (P450(17alpha)), that is, 17alpha-hydroxylase (17alpha-OHase) and 17,20-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel CH,Dhanani S,Owen CP,Ahmed S

更新日期：2006-09-15 00:00:00

abstract：:Two cyclopropanecarbonyl derivatives were independently found to be 15 and 14 times more potent than the corresponding isopropylcarbonyl analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase and dihydroorotate dehydrogenase, respectively. A thorough examination of the co-crystal structures of available enzyme...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kuo PY,Shie TL,Chen YS,Lai JT,Yang DY

更新日期：2006-12-01 00:00:00

abstract：: ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng JH,Hu XL,Lv XY,Wang BL,Lin J,Zhang XQ,Ye WC,Xiong F,Wang H

更新日期：2019-01-15 00:00:00

abstract：:A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY(14) with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gauthier JY,Belley M,Deschênes D,Fournier JF,Gagné S,Gareau Y,Hamel M,Hénault M,Hyjazie H,Kargman S,Lavallée G,Levesque JF,Li L,Mamane Y,Mancini J,Morin N,Mulrooney E,Robichaud J,Thérien M,Tranmer G,Wang Z,Wu J

更新日期：2011-05-15 00:00:00

abstract：:Several boronic acids were screened for their ability to bind to diols. 3-methoxycarbonyl-5-nitrophenyl boronic acid bound to both a catechol dye as well as fructose with a comparable affinity to that of an ortho-methylamino substituted boronic acid. This work suggests a greater role for appropriately functionalized e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mulla HR,Agard NJ,Basu A

更新日期：2004-01-05 00:00:00

abstract：:We aimed to discover a novel type of transient receptor potential vanilloid 1 (TRPV1) antagonist because such antagonists are possible drug candidates for treating various disorders. We modified the structure of hit compound 7 (human TRPV1 IC50=411 nM) and converted its pyrrolidino group to a (hydroxyethyl)methylamino...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takahashi E,Hirano N,Nagahara T,Yoshikawa S,Momen S,Yokokawa H,Hayashi R

更新日期：2013-06-01 00:00:00

abstract：:Reaction of 7-amino-9-ethylguaninium chloride with lead(IV) acetate (LTA) in MeOH yielded 8-aza-9-ethylguanine. Similarly, the reaction of 1-amino-3-methylbenzimidazolium chloride or its substituted derivatives (6-methyl, 5,6-dimethyl and 5-nitro) with LTA gave the corresponding 1-methyl-1H-benzotriazole (or 1-methyl-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaiya T,Aoyama S,Kohda K

更新日期：1999-04-05 00:00:00

abstract：:Further investigation of a series of thienyl-based hydroxamic acids that included ADS100380 and ADS102550 led to the identification of the 5-pyridin-2-yl-thiophene-2-hydroxamic acid 3c, which possessed modest HDAC inhibitory activity. Substitution at the 5- and 6-positions of the pyridyl ring of compound 3c provided c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Price S,Bordogna W,Braganza R,Bull RJ,Dyke HJ,Gardan S,Gill M,Harris NV,Heald RA,van den Heuvel M,Lockey PM,Lloyd J,Molina AG,Roach AG,Roussel F,Sutton JM,White AB

更新日期：2007-01-15 00:00:00